.alpha.-L-Aspartyl-L-phenylalanine methyl ester (hereinafter referred to as "APM") is a useful dipeptide sweetener which is about 200 times sweeter than sugar. APM can be synthesized by various methods. In any of these methods, after purification, crystallization from a hot aqueous solution by cooling is carried out, and the crystalline product is separated from the slurry obtained by solid-liquid separation, for example, using a centrifugal separator, followed by dehydrating and drying to obtain the final product.
Such crystallization by cooling is usually carried out in a stirring type crystallization vessel provided with a heat transfer surface, or in a crystallization vessel equipped with an external circulation type heat exchanger, or in a crystallization vessel in which cooling is effected only by conductive heat transfer, without providing forced flow for the purpose of improving the crystal properties as described in, for example, JP-A-58-177952. (The term "JP-A" as used herein means an "unexamined published Japanese patent application".)
According to JP-A-58-177952, when APM is crystallized by cooling in a crystallization vessel which is accompanied by forced flow such as stirring and external circulation, there are formed fine crystals which exhibit poor filteration and dehydration properties regardless whether the process is continuous or batchwise. In addition, since these crystals readily deposit onto the heat transfer surface and generate a so-called scale thereby rapidly deteriorating the heat transfer efficiency, the crystallization operation must be frequently interrupted to remove the scale.
In order to avoid such problems, the above-cited patent application proposes a method in which an aqueous APM solution is cooled by conductive heat transfer, without providing forced flow such as mechanical stirring, to form a so-called "pseudo-solid phase", followed by further cooling the system, if desired.
By this method, crystals having improved filtration and dehydration properties in the solid-liquid separation step can be obtained. However, this method is poor in efficiency for cooling since the cooling by conductive heat transfer is carried out without stirring and continued even after the "pseudo-solid phase" has been formed.
Such is disadvantageous in the case of crystallizing a substance like APM which is easily decomposed by heat to form non-sweet 5-benzyl-3,6-dioxo-2-piperazine acetic acid (hereinafter referred to as "DKP") and .alpha.-L-aspartyl-L-phenylalanine (hereinafter referred to as "AP").
According to this method, crystallization vessels which are generally used on an industrial scale, such as a vessel type crystallizer, cannot be used, but only special crystallization vessels provided with a large heat transfer surface, from which the "pseudo-solid phase" can be discharged, as proposed in JP-A-58-177952, can be used. As a matter of course, such crystallization vessels are not only poor in cooling efficiency but also expensive, and the crystallization method therefore has disadvantages as an industrial crystallization method.
In order to solve the above-described problems encountered in conventional crystallization methods of APM, the present inventors made extensive and intensive investigations. As a result, it was found that APM is decomposed in a hot aqueous solution to form .alpha.-L-aspartyl-L-aspartyl-L-phenylalanine methyl ester and .beta.-L-aspartyl-L-aspartyl-L-phenylalanine methyl ester (the former being hereinafter referred to as ".alpha.-A.sub.2 PM", the latter as ".beta.-A.sub.2 PM", and the both as "A.sub.2 PM", respectively), in addition to DKP and AP which have hitherto been known to be formed. As a result of further investigations, it was also found that though among these compounds, DKP and AP do not substantially affect the crystallization behavior of APM, A.sub.2 PM causes so-called crystallization inhibition and extremely adversely affects the crystallization behavior of APM.
The inventors made still further investigations based on this finding. As a result, it was found that if crystallization of APM is continuously carried out by cooling while maintaining the content of A.sub.2 PM at a certain level, APM crystals having good filtration and dehydration properties can be formed without substantially generating a scale on the wall and heat transfer surface of a crystallization vessel, under forced flow conditions such as mechanical stirring (see JP-A-3-106899 of some of the present inventors, where this level preliminarily has been described as 150 ppm or less).